In 1851, a coalition in the Massachusetts legislature of Free Soilers and Democrats elected Sumner to fill the U.S. Senate seat of Daniel Webster, who had resigned to become secretary of state.  An opponent of the Compromise of 1850, Sumner tried to repeal its Fugitive Slave Act.  He argued that the intention of the constitutional framers had been to leave the states as the “guardians of Personal Liberty," thus forcing state governments to cooperate in the return of runaway slaves was unconstitutional.  His talent for oratory quickly made him the major antislavery voice in the Senate.  After Congress opened the Western territories to the possibility of slavery in the Kansas-Nebraska Act of 1854, Sumner joined other Free-Soil Democrats and Conscience Whigs to establish the antislavery Republican Party.  

When Kansas became embroiled in violence between pro- and antislavery forces, Sumner delivered a stinging attack from the floor of the Senate.  His speech-“The Crime against Kansas”-used vitriolic rhetoric, focusing particular venom on fellow-Senator Andrew Butler of South Carolina, who was tarred as “mistress” to the “harlot Slavery.”  In retaliation, Butler’s nephew, Congressman Preston Brooks, found Sumner seated at his desk on the Senate floor and beat the senator unconscious with his cane.  The incident raised Sumner to the status of antislavery martyr.  He was absent from the Senate for over three years, yet Massachusetts refused to replace him.  Butler, meanwhile, became a hero to many in the South for upholding the honor of his family and region.  Returning to the Senate in 1859, Sumner continued where he left off with a four-hour antislavery harangue, “The Barbarism of Slavery.”

At the onset of the Civil War Sumner began pushing for emancipation of the slaves.  While lobbying Lincoln for sweeping action, he drafted legislation that undermined the institution of slavery incrementally.  The senator also helped convince the president to use black troops in the Union war effort.  As chairman of the important Senate Foreign Relations Committee, Sumner sparred with Secretary of State William Henry Seward for control of the administration’s foreign policy. 

On the issue of Reconstruction, Sumner was a radical who pushed for treating the former Confederate territory as conquered land to which the federal government could dictate with few restrictions.  He was dissatisfied with Lincoln’s mild reconstruction proposals and later became a chief adversary of President Andrew Johnson’s policies, leading the call for the latter’s impeachment and removal.  Sumner, a key voice for black Americans, drafted or sponsored the major civil rights legislation of the period.

Sumner stood firm against the expansionist and interventionist foreign policy of Republican President Ulysses S. Grant (1869-1877).  He used his chairmanship of the Foreign Relations Committee to stop the Grant administration’s planned annexation of Santo Domingo and their formal recognition of the Cuban faction rebelling against Spanish rule.  In response, the Grant administration orchestrated Sumner’s removal as the committee’s chair. 

Sumner was disgruntled not only by Grant’s foreign policy, but by the president’s hesitancy on civil service reform and the administration’s apparent corruption.  Liberal Republicans pressured the Massachusetts senator to support their rebellion against Grant.  However, Sumner's concern for his own failing health and his urgent desire to secure congressional passage of civil rights and amnesty legislation left him little time or inclination to participate in the movement.  In addition, he feared it could only injure his most cherished objectives if the Liberals aligned later with the Democrats.  Finally, on July 29, Sumner wrote an open letter to black voters, published in newspapers across the country, in which he asked them to support the Greeley ticket.  He then left the United States for a vacation in Europe.